As a result of previous work in this laboratory which demonstrated a difference in the response of adult men and women to dietary PO4 deprivation, the present studies are directed at obtaining more information concerning this difference using an animal model in which the time-course of the response to phosphate deprivation is determined in adult rats of both sexes. These studies would have an advantage over human studies in that it will be possible to directly correlate changes in the plasma level of 1,25-(OH)2-vitamin-D with in vitro measurements of calcium and phosphorus absorption in control versus PO4-deprived males and females. In addition, it will be possible to determine intestinal uptake of 1,25-(OH)2-D in these animals which some workers have proposed is increased during dietary PO4 deprivation, It will also be possible to look for alterations in the metabolism of 25-OH-vitamin D or 1,25-(OH)2-D in these animals by high pressure liquid chromatography. Time-course experiments will also be conducted in calcium-loaded adult female and male rats to determine if there is a sex difference with respect to depression of circulating levels of 1,25-(OH)2-D. Finally, the possibility that the increase in intestinal calcium absorption and plasma 1,25-(OH)2-D levels observed in PO4-deprived animals can be inhibited by an analogue of 1,25-(OH)2-D will also be explored. This is a new area of investigation which may prove useful in the treatment of conditions of 1,25-(OH)2-D overproduction such as idiopathic hypercalciuria.